Urolithin A attenuates RANKL-induced osteoclastogenesis by co-regulating the p38 MAPK and Nrf2 signaling pathway

Wei, Wei; Peng, Chenjian; Gu, Renjun; Yan, Xiwu; Ye, Jiapeng; Xu, Zhuicheng; Sheng, Xianjie; Huang, Guojin; Guo, Yang

doi:10.1016/j.ejphar.2022.174865

Cited by 17 publications

(10 citation statements)

References 25 publications

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“…The hepatoprotective effect was also reported in an acetaminophen hepatotoxicity model in mice, in which urolithin A at intraperitoneal doses of 50, 100, and 150 mg/Kg inhibited oxidative stress accumulation and activated the Nrf2 pathway [154]. Moreover, urolithin A (25 mg/Kg, oral administration) in a model of LPSinduced osteoporosis in C57BL/6 mice attenuated osteoclastogenesis through simultaneous regulating of p28 MAPK and Nrf2 signaling pathways [157].…”

Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 70%

“…The Urolithin A and urolithin B modulate oxidative stress and are recognized as emerging antioxidant coumarin derivatives, reducing ROS generation, free radical scavenging, and activating the Nrf2 signaling pathway through Nrf2 nuclear translocation with further upregulation of HO-1, SOD, glutathione-related antioxidant system, and NQO1 [148]. The antioxidant properties of urolithin A and urolithin B were related to the control of several diseases such as diabetes, skin aging, sclerosis, kidney and liver toxicity, inflammation, and osteoclastogenesis [152][153][154][155][156][157][158][159].…”

Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 99%

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Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Stasi

2023

Pharmaceuticals

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Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor related to stress response and cellular homeostasis that plays a key role in maintaining the redox system. The imbalance of the redox system is a triggering factor for the initiation and progression of non-communicable diseases (NCDs), including Inflammatory Bowel Disease (IBD). Nrf2 and its inhibitor Kelch-like ECH-associated protein 1 (Keap1) are the main regulators of oxidative stress and their activation has been recognized as a promising strategy for the treatment or prevention of several acute and chronic diseases. Moreover, activation of Nrf2/keap signaling pathway promotes inhibition of NF-κB, a transcriptional factor related to pro-inflammatory cytokines expression, synchronically promoting an anti-inflammatory response. Several natural coumarins have been reported as potent antioxidant and intestinal anti-inflammatory compounds, acting by different mechanisms, mainly as a modulator of Nrf2/keap signaling pathway. Based on in vivo and in vitro studies, this review focuses on the natural coumarins obtained from both plant products and fermentative processes of food plants by gut microbiota, which activate Nrf2/keap signaling pathway and produce intestinal anti-inflammatory activity. Although gut metabolites urolithin A and urolithin B as well as other plant-derived coumarins display intestinal anti-inflammatory activity modulating Nrf2 signaling pathway, in vitro and in vivo studies are necessary for better pharmacological characterization and evaluation of their potential as lead compounds. Esculetin, 4-methylesculetin, daphnetin, osthole, and imperatorin are the most promising coumarin derivatives as lead compounds for the design and synthesis of Nrf2 activators with intestinal anti-inflammatory activity. However, further structure–activity relationships studies with coumarin derivatives in experimental models of intestinal inflammation and subsequent clinical trials in health and disease volunteers are essential to determine the efficacy and safety in IBD patients.

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Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 70%

Section: Intestinal Anti-inflammatory Gut Microbial Coumarins Targeti...mentioning

confidence: 99%

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Stasi

2023

Pharmaceuticals

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“…Hence, the effects of phenols on RANKL and its downstream pathways have gained considerable interests. Investigations on carnosic acid, paeonol and ellagic acid indicated that phenols blocked classical pathways (Nrf-2/NF-κB and MAPK/JNK/ERK/p38 pathways) to prevent macrophages from differentiating into osteoclasts [ 52 , [77] , [78] , [79] , [80] , [81] , [82] , [83] ]. Additionally, the Akt/Btk-PLCγ2 and Blimp1 signals, which played a promotive role in the synthesis of c -Fos/NFATc1, were suppressed by methyl gallate and agrimohol without involving classical pathways, suggesting extra suppressive avenues of phenols on osteoclastogenesis [ 84 , 85 ].…”

Section: Phenolic Compounds Regulate Btcsmentioning

confidence: 99%

Plant molecules reinforce bone repair: Novel insights into phenol-modified bone tissue engineering scaffolds for the treatment of bone defects

Chen,

Gan,

Cheng

et al. 2024

Materials Today Bio

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“…The trial duration was too short to assess BMD changes. However, several preclinical studies have demonstrated an inhibition of osteoclastogenesis and a decrease in experimental bone loss, raising some hope on the effect of urolithin A on bone health [ 49 , 50 ].…”

Section: Gut Microbiotamentioning

confidence: 99%

Bone health: biology and nutrition

Rizzoli,

Chevalley

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Recent findings in the influence of dietary patterns, dairy products, beverages and microbiota composition and function on bone health are reviewed and discussed. Recent findings Evidence is accumulating on the increased risk of fracture in individuals following a vegan diet. Meta-analysis of randomized controlled trials indicates a favourable, though of low amplitude, effect of dairy products on bone mass accrual during childhood and adolescence. Though mostly based on results from observational studies, it seems that dairy product consumption, particularly fermented dairy products, is associated with a lower risk of hip fracture. Regular green tea drinkers may have a lower fracture risk than tea abstainers. Magnesium intake is beneficial for bone health. Prune supplements prevents bone loss in untreated postmenopausal women. This seems to be associated with modification of gut microbiota. Summary This information should help the medical practitioners facing questions from their patients on how to protect bone health through nutrition.

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Urolithin A attenuates RANKL-induced osteoclastogenesis by co-regulating the p38 MAPK and Nrf2 signaling pathway

Cited by 17 publications

References 25 publications

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

Plant molecules reinforce bone repair: Novel insights into phenol-modified bone tissue engineering scaffolds for the treatment of bone defects

Bone health: biology and nutrition

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